DRHOOK- Crestor smile: Drug slashes health risks
Cheeseburgers, French fries, and BBQ potato chips would be my choice of foods if I were stuck on a desert island. (Hmm, sounds like Lost.) After all, my health would be my last concern if I were destined to live the rest of my life on a lonely island.
But I know some people right here in the middle of civilization who just don't care about their high cholesterol. One dude said to me there was no proof that high cholesterol is associated with heart attacks or strokes. (I also know people who don't think HIV causes AIDS.)
Many credible studies have shown that high cholesterol increases the risk of cardiovascular problems– but even Christopher Columbus didn't convince everyone the world was round.
Does cholesterol-lowering medicine save lives?
Crestor is a statin drug that is very powerful in lowering LDL, the bad cholesterol. For some funny reason, all the Crestor studies are titled with an outer space name. The "Meteor" study showed how Crestor reduces atherosclerosis in the carotid arteries (something most other cholesterol-lowering medicines can't claim). There is even a "Uranus" study (but that sounds more like a proctology investigation).
Now the "Jupiter" study is in the New England Journal of Medicine. This study was very impressive, and I don't have any financial ties with AstraZeneca.
I did an epidemiological review on the "Jupiter" study for Crestor, and it was done well. This study was actually stopped early– after a median of 1.9 years– because the study strongly showed the drug saves lives– more than any other lipid-lowering study has ever shown.
It was a very large double-blind, placebo-controlled, randomized clinical trial involving over 17,000 participants in 26 countries. The folks were mostly white men, but still a good percentage of women (38 percent) and non-white (29 percent).
In general, the folks were overall healthy, meaning they hadn't had a cardiovascular problem like a heart attack or stroke. Their problem was an elevated high sensitivity C-Reactive Protein (CRP). CRP is measured in the blood and is associated with heart disease.
Well, of course, in this day and age, most of the folks were overweight and 41 percent had Metabolic Syndrome X (big belly, high blood pressure, glucose intolerance). But these folks didn't have a high LDL, and so they were never on cholesterol medicine.
Guess what? The folks taking Crestor 20mg a night had 56 percent fewer major cardiovascular events than the folks taking a placebo, with a major statistical significance. In epidemiology, a 56 percent benefit is like winning by 100 points at the Super Bowl. (I can't believe I just used a football analogy.)
Showing more than a 20 percent benefit is hard to do in research. So it's amazing that Crestor showed 46 percent benefit in reducing fatal and nonfatal heart attacks, 52 percent benefit in fatal and nonfatal strokes, and 20 percent benefit of death for any reason at all. (Hmm, I'm tempted to eat a cheeseburger everyday while on Crestor, but I won't. Sigh.)
Also there's a question of how much money will be saved by Crestor's preventing cardiac interventions (such as stents and angioplasties) because there was a 53 percent benefit in the conditions that lead to those interventions.
There wasn't increased muscle breakdown or liver toxicity on Crestor, though as with other statins there seems to be a slight increase in developing diabetes.
I find it interesting when a drug has amazing results, it is touted as a "class effect" (i.e. all statins have the same benefit), but if there's a bad side effect, it's then considered a "specific drug problem" (like only Drug X is dangerous. We ain't! No, sir-ee!)
But as significant as the "Jupiter" study is compared to any other cholesterol-lowering study, I think it‘s going to be pretty hard to beat Crestor.
Dr. Hook cracks a joke or two, but he's a renowned physician with a local practice. Email him with your questions.
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7 comments
Dr. Hook, Why are clinical trial numbers reported in "relative risks" vs "absolute risks"? And why is NNT not included? The accompanying editorial about the JUPITER trial in the NEJM written by Dr. Mark Hlatk,(N Engl J Med 359:2280, November 20, 2008) noted the NNT for 1.9 yrs(number of patients needed to be treated for 1.9yr): for 1 person to avoid a cardiovascular event, 120 patients had to take Crestor for 1.9 yrs. Since you performed the statistical analysis, I am sure you are aware of the increased rate of diabetes which occurred in the Crestor group. 3.0% vs 2.4%. Lest that sound insignificant, the real percentages of the decrease in overall Cardiovascular events were 2.8% in the placebo group and 1.6% in the Crestor group. The decrease in the most serious events, including those that were fatal and heart attack and strokes events was 1.7% in placebo group vs 0.9% in the Crestor group. Those % es are translated into the relative risks reported of "56% and 42% decreases" in cardiovascular events with Crestor. Taking Crestor to prevent 1 cardiovascular event works out to costing $285,000 (120 persons taking Crestor @ $3.45/day for 1.9 yrs). And as Merrill Goozner noted in his article analyzing this study "...for every person who didn't get a serious cardiovascular event, three-quarters of a person got diabetes"
http://www.gooznews.com/archives/001243.html
If the objective for this study was that statins, esp. Crestor, are good for primary prevention (ie for individuals who have not suffered a cardiac event)I am not even remotely convinced. That 119 people must take a statin for 1.9 yrs and be exposed to all the potential adverse effects of this class of drugs (which are not inconsequential)for one person to benefit, is not a reassurring # to me. Thank you, I will continue eating oatmeal with cinnamon, limiting red meats, and exercising, and avoiding myalgias that could lead to immobility, abnormal liver function tests and thus liver problems, severe headaches, visual problems, cognitive decline and all the other potential side and adverse effects listed for statins.
How can we continue to countenance Mevlonate Blockading drugs in anything other than short term emergency use.
In the longer term (longer than most trials) the all mortality and ADR outcomes are appalling. Pfizer's withdrawal from such treatments has less to do with patents and more to do with the coming storm of litigation over excessive use of statins.
Be very careful using this class of drugs
(I also know of idiot doctors who will never admit that U.S. Government scientists created the A.I.D.S. virus in a laboratory, and who lovingly gobble up GMO food and chug fluorinated water for breakfast. I even know idiot doctors who will lock you up and torture you for even suggesting such. Here's a brief, non-comprehensive list of them: Collen Slipka, Jonathan Anderson, Barry Blumenthal. visit www.infowars.com and LISTEN TO THE ALEX JONES SHOW - YOU'LL LEARN MORE INFORMATION WHICH YOU NEED TO KNOW THAN YOU EVER WILL AT ANY COLLEGE OR UNIVERSITY
Oops, I left an "e" out of one of the idiot doctors' first names. Oh, well.
Such negativity for a landmark trial. I thought the trial was important in understanding more about CHD and why it is still the #1 killer in America. Here was a group of patients who normally would not be treated, and it cut mortality in half. And for those whom like to focus on the small absolute differences, may I remind you that the absolute numbers for the ASCOT trial were very similar, along with many other outcomes trials for other statins. Do your homework. Moreover, other statin outcomes trials have shown increases in diabetes, increases in cancer death, decreases in cancer death as in Jupiter, etc. Physician reported diabetes (was that pre-diabetes? 100-126 glucose?)with no defining criteria, with no change in glucose levels or A1C between groups is a question mark in itself. I think if these trials were repeated with a different subset of patients, these numbers would be subject to change. Regardless, I think this was a great trial and shed new light on a grim subject of a disease that continues to kill more people than 5 of the top cancers combined.
I would have to agree with kls341, although eml256 does have some good points. Overall, if you look at other mortality trials containing thousands of patients, the absolute % risk reduction differences are within 1-3% across the board. Another trial that was similar to Jupiter due to the fact that it was stopped short was the atorvastatin ASCOT trial. ASCOT absolute % risk reduction for the primary endpoint was 2.9% (placebo) vs. 1.9% (atorvastatin), which was indeed very similar to the Jupiter trial of 2.8% vs. 1.6%. The fewer the years in a trial, the fewer mortalities. Jupiter was stopped after 1.9 years, and ASCOT was stopped after 3.3 years. I think the NNT number for projected 5 years for Jupiter was somewhere around 25, which is up there with most large secondary prevention trials.
Another thing to point out is the relative risk reduction of 44%; find me another outcomes trial that can beat it, because I could not find one.
I think that the sicker (higher risk, higher LDL) the patients are in a mortality trial, the higher the probablity that 1) you will have more CV related deaths and events, and 2) better effects with statin treatment. Are we then comparing apples to oranges here?
The Jupiter trial was indeed an interesting addition to the medical community and also showed that Crestor, too, saves lives. I don't think the idea here is that, "Everyone should be on a statin as a primary preventative treatment." But I do think it has opened some eyes as to the severity of CHD, and how important it is to fully evaluate risk factors, most importantly: family history. hsCRP, in my eyes, is another tool in the tool box, along with CIMT, homocysteine, fibrinogen, LP(a), Apo E, A, B . . . and the list just keeps getting longer as we learn more about the importance of NOT taking this disease lightly.
Recently I had my blood work draw, I fasted for 12 hrs. I take crestor (1)20mg. per night along w/ 100mg of 5 htp per night. my question is can either of these pills increase my glucose level? cause my fasten glucose was 115 level.I did take both pills crestor & 5 htp before bedtime.